While the IGF1/FoxO1/mTORC1 signalling pathway is a well‐established nutrigenomic link between high glycaemic index (GI)/glycaemic load (GL) diet and acne vulgaris, other signalling pathways remain elusive. Therefore, we aimed to investigate other genes that are involved in the high GI/GL diet‐acne link, using our Singapore/Malaysia population epidemiological, genomics and transcriptomics data. High GI/GL dietary habit of 3207 acne cases (1869 and 1341 further classified into severity and scarring grades, respectively) and 2521 controls were evaluated based on Quality of Diet based on Glycaemic Index Score (QDGIS). Overlapping concordant differentially expressed genes (DEGs) between acne case–controls and QDGIS poor‐moderate/good classes were identified from whole‐transcriptome sequencing data of PBMC of a subset of participants. Finally, we assessed the expression quantitative trait loci (eQTL) association of single nucleotide polymorphisms (SNPs) of the concordant DEGs. Daily intake of fruits significantly reduced the risk of acne presentation, severity and scarring by up to 48.5%. Those with good QDGIS had significantly lower risk of mild and moderate/severe acne, and grade 1/2 acne scarring. Sequential filtering identified four overlapping concordant DEGs that were significantly associated with acne and QDGIS, namely GOLGA7B, SNCB, LOC102723849 and LOC283683. Combining transcriptome and genetic association data, we identified intronic SNP rs1953947 in GOLGA7B as an eQTL for acne. In conclusion, we identified GOLGA7B as a plausible novel gene that links high GI/GL with acne, and hence propose a model for the involvement of Golga7b in high GI/GL diet‐acne pathogenesis, which includes palmitoyl acyltransferase zDHHC5, fatty acid translocase CD36 and palmitic acid.

<b><i>Introduction:</i></b> Previous studies have indicated the <i>ERBB2</i> genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated <i>ERBB2</i> single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. <b><i>Methods:</i></b> This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on <i>n</i> = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. <b><i>Results:</i></b> The <i>ERBB2</i> tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele “G” identified as protective against the disease (adjusted logistic <i>p</i> = 6.56 × 10⁻⁹, OR = 0.625, 95% CI: 0.544–0.718). The allele “G” of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (<i>p</i> &lt; 0.001), whereas the overall <i>ERBB2</i> mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype “GG” of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. <b><i>Conclusions:</i></b> The present findings highlighted the involvement of a functional exonic variant of <i>ERBB2</i> in asthma development via modulating the MAPK signaling cascade.

Background:Elaeis guineensis (oil palm) pollen is one of the most predominant species of inhalant allergens in the tropical Southeast Asia region; however, its association with the manifestation of allergic diseases remains largely unexplored. We aimed to determine the sensitization pattern of oil palm pollen and associate this with the risk and severity of allergic diseases. Methods: Participants were recruited as a part of the Singapore and Malaysia cross-sectional genetic and epidemiological study (SMCSGES). Two independent cohorts were recruited: n=564 serum samples were collected and serological assessment was performed against a panel of 16 crude inhalant allergens including house dust mite, pet, insect, pollen, and fungal allergens; n=13,652 Singapore/Malaysia Chinese young adults were recruited and skin prick test was used to assess oil palm sensitization, which was tested for its association with the risk and severity of asthma, allergic rhinitis (AR), and atopic dermatitis (AD). Results: The sensitization rate of oil palm pollen is 9.6% in the n=564 Singapore/Malaysia cohort. In the n=13,652 Singapore/Malaysia Chinese cohort, oil palm sensitization significantly associates with increased risks of asthma ( p=1.34x10 ), AR ( p=2.91x10 ), and AD ( p=6.95x10 ). Asthmatic patients with oil palm sensitization have increased risks of wheezing ( p=0.00995), nocturnal cough ( p=0.0122), and exacerbations ( p=0.00139) in the past 12 months. AR patients with oil palm sensitization also have an increased risk of developing moderate-to-severe symptoms ( p=0.00113). Conclusions: We have identified significant associations of oil palm sensitization with increased risks, exacerbations, and the severity of symptoms of allergic diseases in the tropical Southeast Asian region (Singapore/Malaysia).